Dobutamine, (.+-.)-N-[3-(4-hydroxyphenyl)-1-methylpropyl]2-(3,4-dihydroxyphenyl) ethylamine is marketed as the hydrochloride salt under the trademark Dobutrex.RTM.. The use of dobutamine as an inotrope useful for treating cardiac insufficiency is disclosed and claimed in U.S. Pat. No. 3,987,200 which describes only mineral acid salts of dobutamine. Kulz, U.S. Pat. No. 2,273,619, discloses a higher homologue of dobutamine, N-[3-(4-hydroxyphenyl)-1-methylpropyl]-1-methyl-2-(3,4-dihydroxyphenyl) ethylamine (Example 1) and an isomer, N-[3-(4-hydroxyphenyl) propyl 1-methyl-2-(3,4-dihydroxyphenyl)ethylamine (Example 2). Only the hydrobromide salts were prepared. Blout et al., U.S. Pat. No. 2,949,359, describe some related compounds including, for example, N-[2-(2,5-dihydroxyphenyl) ethyl-1-methyl-2-(2,5-dihydroxyphenyl)-ethylamine useful in a process for developing photo-sensitive silver halide emulsions. The hydroxyls in the phenyl rings must be ortho or para since oxidation to a quinhydrone or quinone is a requirement for use in such a method. Suh, U.S. Pat. No. 3,932,461 (Suh I) discloses N-[3-(3,4 -methylenedioxyphenyl)-1-methylpropyl 2-(3,4-dihydroxyphenyl)ethylamine. Several organic salts are mentioned, including the tartrate. The compounds are said to be depressants or analgesics and to have cardiotonic properties similar to those ascribed to dobutamine (increased contractile force without significant effect on blood pressure or heart rate). No special problem of solubility of the various disclosed salts is mentioned. Another Suh patent, U.S. Pat. No. 3,700,692 (Suh II), discloses similar compounds containing a .beta.-hydroxyethyl-.beta.-(3,4-dihydroxyphenyl)-ethylamine moiety. Biel, U.S. Pat. No. 3,139,441, is another reference disclosing .beta.-hydroxy-ethylamines. Such compounds are derived from norepinephrine rather than dopamine. Finally, Ariens, Proc. Inter. Pharmacol. Meeting (Stockholm) 7, 247-64, describes the testing on .alpha. and .beta.-receptors of both the norepinephrine-type compounds (Table 1) and the dopamine-type compounds (part of Table III), containing in each instance a 1-methyl-2-(4-hydroxyphenyl)ethyl group attached to an amine group. Salts are not mentioned.
None of the above references relate to the problem of the insolubility of mineral acid salts of dobutamine or of related secondary amines; and none teach the advantageous properties of dobutamine salts formed with certain classes of hydroxyalkanoic acids.